8Y3U

Ebola virus glycoprotein in complex with a broadly neutralizing antibody 2G1

Summary for 8Y3U

• Entry DOI: 10.2210/pdb8y3u/pdb
• EMDB information: 38899
• Descriptor: 2G1 VH, 2G1 VL, Virion spike glycoprotein, ... (5 entities in total)
• Functional Keywords: antiviral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 160968.36

Authors

Fan, P.F.,Yu, C.M.,Chen, W. (deposition date: 2024-01-29, release date: 2024-08-07, Last modification date: 2025-02-19)

Primary citation

Fan, P.,Sun, B.,Liu, Z.,Fang, T.,Ren, Y.,Zhao, X.,Song, Z.,Yang, Y.,Li, J.,Yu, C.,Chen, W.
A pan-orthoebolavirus neutralizing antibody encoded by mRNA effectively prevents virus infection.
Emerg Microbes Infect, 13:2432366-2432366, 2024

PubMed Abstract: is a genus of hazardous pathogens that has caused over 30 outbreaks. However, currently approved therapies are limited in scope, as they are only effective against the Ebola virus and lack cross-protection against other orthoebolaviruses. Here, we demonstrate that a previously isolated human-derived antibody, 2G1, can recognize the glycoprotein (GP) of every orthoebolavirus species. The cryo-electron microscopy structure of 2G1 Fab in complex with the GPΔMucin trimer reveals that 2G1 binds a quaternary pocket formed by three subunits from two GP protomers. 2G1 recognizes highly conserved epitopes among filoviruses and achieves neutralization by blocking GP proteolysis. We designed an efficient mRNA module capable of producing test antibodies at expression levels exceeding 1500 ng/mL in vitro. The lipid nanoparticle (LNP)-encapsulated mRNA-2G1 exhibited potent neutralizing activities against the HIV-pseudotyped Ebola and Sudan viruses that were 19.8 and 12.5 times that of IgG format, respectively. In mice, the antibodies encoded by the mRNA-2G1-LNP peaked within 24 h, effectively blocking the invasion of pseudoviruses with no apparent liver toxicity. This study suggests that the 2G1 antibody and its mRNA formulation represent promising candidate interventions for orthoebolavirus disease, and it provides an efficient mRNA framework applicable to antibody-based therapies.

PubMed: 39560055
DOI: 10.1080/22221751.2024.2432366

Experimental method

ELECTRON MICROSCOPY (2.98 Å)